Recent studies have demonstrated that dopamine can be internalized and stored in association with prolactin-containing vesicles in the anterior pituitary gland. It has been suggested that this incorporation of dopamine in the lactotroph may mediate at least part of the inhibitory role of this amine on prolactin secretion. There is a disruption of this dopamine internalization and storage mechanism in the aged rat which is temporally related to an increased anterior pituitary secretion of prolactin. Despite the apparent age-induced reduction of tuberoinfundibular dopamine neuronal function, the concentration of dopamine in the anterior pituitary, which is believed to represent amine released from the neurons, progressively increases in intermediate age and aged rats. The maintenance of high prolactin secretion despite the elevated content of dopamine in the anterior pituitary suggests an age-related defect in the dynamics of dopamine in this gland; this defect may contribute to the loss of reproductive function in the aging rat. The primary objective of the proposed project is to examine the dynamics of dopamine internalization and storage in the anterior pituitary of the aged rat and to relate changes in these dynamics with alterations in prolactin secretory mechanisms. Proposed studies will utilize microbiochemical techniques to determine if the age-related changes in anterior pituitary prolactin secretion is the result of a disruption of pituitary dopamine internalization, storage, metabolism and/or function (i.e., inhibition of prolactin release and/or synthesis, stimulation of lysosomal activity, actions on adenylate cyclase).